RESUMEN
The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a "one-step" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.
Asunto(s)
Neoplasias de la Mama , Curcumina , Nanopartículas , Óxido Nítrico , Curcumina/farmacología , Curcumina/administración & dosificación , Curcumina/química , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Nanopartículas/química , Animales , Humanos , Óxido Nítrico/administración & dosificación , Óxido Nítrico/metabolismo , Óxido Nítrico/química , Ratones , Lípidos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Carbonato de Calcio/química , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Arginina/químicaRESUMEN
Larotrectinib (Lar) is an orally administered tropomyosin receptor kinase (Trk) inhibitor with broad-spectrum antitumor activity that is available in clinical dosage forms as capsules and oral solutions. Currently, corresponding research is focused on developing new extended-release formulation systems for Lar. In this study, a biocompatible Fe-based metal-organic framework (Fe-MOF) carrier was synthesized by a solvent-based method, and a sustained-release drug delivery system (Lar@Fe-MOF) was constructed by nanoprecipitation and Lar loading. Lar@Fe-MOF was characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA), and its drug loading capacity and drug release properties were measured by ultraviolet-visible (UV-vis) spectroscopy. Then, the toxicity and biocompatibility of the Fe-MOF carriers were evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and hemocompatibility assays. Finally, the anticancer potential of Lar@Fe-MOF was investigated. The TEM results showed that Lar@Fe-MOF had a homogeneous fusiform nanostructural morphology. The DSC and FTIR results showed that Fe-MOF carriers were successfully synthesized and loaded with Lar, which was mainly in an amorphous form. Lar@Fe-MOF showed a large drug loading capacity (-10%) and significant slow-release properties in vitro. The MTT assay results showed that Lar@Fe-MOF had good dose-dependent anticancer activity. The in vivo pharmacodynamic assay results showed that Fe-MOF significantly increased the anticancer activity of Lar and was biocompatible. In conclusion, the Lar@Fe-MOF system developed in this study is a promising drug delivery platform because it is easy to manufacture, has high biocompatibility and ideal drug release and accumulation, can effectively eliminate tumors with improved safety and is expected to further expand therapeutic applications.
RESUMEN
Breast cancer is prevalent and diverse with significantly high incidence and mortality rates. Curcumin (Cur), a polyphenol component of turmeric, has been widely recognized as having strong anti-breast cancer activity. However, its anti-cancer efficiency is largely impaired by some of its concomitant negative properties, including its poor solubility, low cellular uptake, and severe reported side effects. Hence, the necessity arises to develop a novel low-toxic and high-efficiency targeting drug delivery system (DDS). In this study, we developed a pH-sensitive tumor self-targeting DDS (Cur@HFn) based on self-assembled HFn loaded with Cur, in which Cur was encapsulated into HFn cavity by using a disassembly/reassembly strategy, and the Cur@HFn was characterized by ultraviolet-visible (UV-vis), dynamic light scattering (DLS), and transmission electron microscope (TEM). A variety of breast cancer cell models were built to evaluate cytotoxicity, apoptosis, targeting properties, and uptake mechanism of the Cur@HFn. The pharmacodynamics was also evaluated in tumor (4T1) bearing mice after intravenous injection. In vitro release experiments showed that Cur@HFn is pH sensitive and shows sustained drug release under slightly acidic conditions. Compared with Cur, Cur@HFn has stronger cytotoxicity, cellular uptake, and targeting performance. Our study supported that Cur@HFn has a higher in vivo therapeutic effect and lower systemic toxicity. The safety evaluation results indicated that Cur@HFn has no hematotoxicity, hepatotoxicity, and nephrotoxicity. The findings of the present study showed that the Cur@HFn has been successfully prepared and has potential application value in the treatment of breast cancer.
Asunto(s)
Neoplasias de la Mama , Curcumina , Animales , Apoferritinas , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Portadores de Fármacos/química , Femenino , Humanos , Concentración de Iones de Hidrógeno , RatonesRESUMEN
Artesunate was reported to have inhibition effect on tumors via amplified oxidative stress while the lack of intratumoral ferrous ions supply greatly hinders its efficacy. Herein, the AS/GOD@HAZnO NPs we proposed could be efficiently taken in by the affinity between hyaluronic acid and the CD44 receptors. DLS and TEM results manifested the nano-size (~ 160 nm) and circular shape of AS/GOD@HAZnO NPs. Due to the acid-responsive degradation, AS/GOD@HAZnO NPs realized responsive release (up to 80%) in acid environment while only 20% was released in neutral medium. The cellular and in vivo experiment showed that co-delivery of AS and GOD via HAZnO NPs could effectively induce the overproduction of ROS and cut the glucose supply of tumor cells, and thus result in efficient cell apoptosis and tumor inhibition.
Asunto(s)
Nanopartículas , Neoplasias , Óxido de Zinc , Línea Celular Tumoral , Humanos , Ácido Hialurónico , Neoplasias/patología , Estrés Oxidativo , Óxido de Zinc/farmacologíaRESUMEN
Osteoarthritis (OA) is a common joint disease characterized by cartilage degradation. Chondroitin sulfate from shark (CS-S) has a good effect on OA in clinical, but due to source limited of CS from shark. Therefore, it is important to find a novel CS source with similar efficacy to CS-S in the treatment of OA. Herein, we reported a therapeutic effect of CS from scophthalmus maximus (CS-SM) for treating OA in rats. The OA model was established. After intervention with CS-SM by intragastric administration. Our results showed that CS-SM could protect articular cartilage in OA, inhibit the degradation of cartilage, decrease the apoptosis of chondrocytes, decline the content of interleukin-1, tumor necrosis factor-α and Prostaglandins E2 in synovial fluid, down-regulate the protein expression of matrix metalloproteinase-1 and up-regulate the protein expression of tissue inhibitor of metalloproteinase-1. Our results suggest that oral CS from SM is a new potential therapy for OA.